Pleural effusion is a complicating feature of many diseases of the lung and pleura, but its effects on the mechanics of the diaphragm have not been assessed. In the present study, radiopaque markers were attached along muscle bundles in the midcostal region of the diaphragm in anesthetized dogs, and the three-dimensional location of the markers during relaxation before and after the stepwise introduction of liquid into the left or right pleural space and during phrenic nerve stimulation in the same conditions was determined using computed tomography. From these data, accurate measurements of diaphragm muscle length and displacement were obtained, and the changes in pleural and abdominal pressure were analyzed as functions of these parameters. The effect of liquid instillation on the axial position of rib 5 was also measured. The data showed that 1) liquid leaked through the dorsal mediastinal sheet behind the pericardium so that effusion was bilateral; 2) effusion caused a caudal displacement of the relaxed diaphragm; 3) this displacement was, compared with passive lung inflation, much larger than the cranial displacement of the ribs; and 4) the capacity of the diaphragm to generate pressure, in particular pleural pressure, decreased markedly as effusion increased, and this decrease was well explained by the decrease in active muscle length. It is concluded that pleural effusion has a major adverse effect on the pressure-generating capacity of the diaphragm and that this is the result of the action of hydrostatic forces on the muscle.